An NMR apparatus is most often characterized in gross by cylindrical symmetry. A typical NMR magnet is of the superconducting variety and is housed in a dewar which includes a room temperature cylindrical bore in which a very carefully controlled homogeneous magnetic field is sustained by operation of the superconducting magnet in the interior of the dewar. An NMR probe holds a sample placed in the uniform magnetic field. The housing for the probe is typically cylindrical to fit within the bore of the magnet and the sample is generally positioned along the central axis of the probe. A coil is disposed close to the sample within the probe to apply an exciting radio frequency (RF) magnetic field to the sample. The resultant resonance signal of the sample is picked up by the coil and delivered to a receiver circuit. The receiver circuit generates an output signal. A computer takes the Fourier transform of the signal to obtain an NMR spectrum.
HPLC is widely used to separate organic mixtures for analysis. Although ultraviolet, infrared and mass spectroscopy have been used for qualitative analyses of HPLC eluents, NMR spectroscopy generally provides unequaled structural information and has sample requirements more reasonably matched to HPLC. Efforts to couple these two analytical techniques, however, have been hampered by the low sensitivity of the NMR detector. Recent improvements in NMR detection cells for use in flow-through NMR probes have allowed for high resolution, high sensitivity and ease of use in HPLC-NMR coupled analyses. See, for example, U.S. Pat. No. 5,867,026, entitled "Flow Tube for NMR Probe" disclosing an improved flow-through NMR detection cell and method of manufacture. Such improved flow tube designs have led to increased acceptance and usage of sample placement for NMR spectrometers using fluid injection methods and have created further interest in flow-based automatic sample measurement. As these techniques become more routinely used and accepted, the minimization of downtime for the NMR and the optimization of system performance for efficient measurement throughout become increasingly advantageous.
Current NMR flow tube assemblies, including the NMR sample flow tube together with its various connectors and associated tubing for attachment to an HPLC, are delicate, difficult to handle and not well suited for exchange in the field. Removal and insertion of such assemblies in the NMR probe is risky and expensive, at least in part because the flow tubes (and attached connectors) are positioned and secured to the NMR probe within nested assemblies of coils, dewars, and support structures. Many present designs require significant mechanical interaction with these closely mated subassemblies. Electrical manipulations are often needed to exchange the flow tube, such as unsoldering and resoldering of the RF and pulsed field gradient coils. Some designs have RF circuitry directly attached and secured to the flow tubes. There is an additional cost and risk associated with exchange of the flow tube in these designs because of the directly secured RF circuitry.
Other flow tube assembly designs that promise exchangeability of the NMR flow tube require significant modification of the NMR probe or subassemblies to accommodate the removable flow tube. Such designs generally utilize fully integrated flow tube assemblies having parts and associated tubing that are permanently bonded together with chemical adhesives. See, e.g., Barjat et al., "Adaptation of Commercial 500 MHz Probes for LCNMR," Journal of Magnetic Resonance, Series A 119, 115-119 (1996). These NMR flow tubes offer the advantage of a high filling factor due to their slender construction and consistent outside diameter, however, such fully assembled and permanently bonded structures do not allow rapid exchange of the flow tube or associated tubing, for cleaning or optimizing individual applications. They also lack mechanical reproducibility due to difficulties in controlling the adhesive-assembly process. Moreover, the possibility of contact between the analytical solutions and the adhesives used in bonding the parts of fully such integrated assemblies can cause chemical compatibility problems and sample contamination.
Ease-of-exchange of the NMR flow-tube is important. Users often wish to change or exchange the flow tube assembly since flow tubes and attached tubing can become clogged over time or reach the point where cleaning protocols are insufficient. The flow tubes or tubing may break and require replacement or the user may wish to incorporate a post-probe sample collector. Moreover, users may wish to optimize the sample chamber of the flow tube for various applications, for example, if research shifts to samples where quantities are limited. What is needed is an NMR flow tube assembly of inert construction that permits the simple and efficient removal and insertion of an NMR flow tube in a flow-through NMR probe with a minimum amount of probe modification while maintaining a high filling factor.